List of diseases with a known mechanism but no cure/treatment

J

Jaybee00

Senior Member (Voting Rights)
Posting this for those who believe it will be easy to find a cure for MECFS once a mechanism is found.


From Chat GPT


Here’s a list of diseases with a well-understood mechanism but no cure or effective treatment:


Neurodegenerative Diseases:

1. Alzheimer’s disease – Progressive neurodegeneration due to amyloid-beta plaques and tau tangles.

2. Parkinson’s disease – Dopaminergic neuron loss in the substantia nigra due to α-synuclein aggregation.

3. Amyotrophic lateral sclerosis (ALS) – Motor neuron degeneration linked to SOD1, TDP-43, and FUS protein dysfunction.

4. Huntington’s disease – Genetic disorder caused by CAG repeat expansion in the HTT gene, leading to toxic huntingtin protein.

5. Frontotemporal dementia (FTD) – Neuronal loss due to tau and TDP-43 protein aggregation.


Genetic and Metabolic Disorders:

6. Progeria (Hutchinson-Gilford Progeria Syndrome) – Caused by a mutation in the LMNA gene, leading to accelerated aging.

7. Friedreich’s ataxia – Expansion of GAA repeats in the FXN gene leads to mitochondrial dysfunction and neurodegeneration.

8. Tay-Sachs disease – Deficiency of hexosaminidase A results in GM2 ganglioside accumulation in neurons.

9. Spinal muscular atrophy (SMA) type 1 – Mutation in the SMN1 gene leads to motor neuron degeneration. (Some treatments like gene therapy exist but are not cures.)

10. Cystic fibrosis (CF) – Mutations in the CFTR gene cause thick mucus buildup, leading to respiratory failure. (Treatments exist but no cure.)


Autoimmune & Inflammatory Diseases:

11. Type 1 diabetes – Autoimmune destruction of pancreatic beta cells leads to insulin deficiency.

12. Multiple sclerosis (MS) – Autoimmune attack on myelin in the central nervous system causes neurological dysfunction.

13. Lupus (Systemic Lupus Erythematosus, SLE) – A systemic autoimmune disease where the immune system attacks tissues and organs.


Infectious Diseases (Chronic & Incurable):

14. HIV/AIDS – HIV attacks CD4+ T cells; treatments exist (ART) but no cure.

15. Prion diseases (e.g., Creutzfeldt-Jakob disease, Fatal Familial Insomnia) – Misfolded prion proteins cause fatal neurodegeneration.

16. Herpes simplex virus (HSV-1 & HSV-2) – Establishes lifelong latency in neurons; no cure.


Cancer (Certain Types Without Effective Treatment):

17. Glioblastoma – Highly aggressive brain cancer with rapid progression and poor survival rates.

18. Pancreatic cancer (late-stage) – Often diagnosed too late for effective treatment.

19. Diffuse intrinsic pontine glioma (DIPG) – A fatal pediatric brainstem tumor with no effective treatment.


Miscellaneous Rare Diseases:

20. Idiopathic pulmonary fibrosis (IPF) – Progressive lung scarring with unknown cause and no cure.

21. Fibrodysplasia ossificans progressiva (FOP) – Mutation in ACVR1 gene causes soft tissue to turn into bone.


These diseases have known biological mechanisms but currently lack a cure or fully effective treatment. Some, like HIV and cystic fibrosis, have treatments that manage symptoms but do not eliminate the disease.
 
Here is deep seek


Certainly! Here is a list of diseases where the underlying mechanism is well-understood (or at least partially understood), but there is currently no effective treatment or cure:

### **Neurodegenerative Diseases**
1. **Alzheimer’s Disease** – Mechanisms include amyloid-beta plaques, tau tangles, and neuroinflammation, but no disease-modifying treatments exist.
2. **Parkinson’s Disease** – Dopaminergic neuron loss and alpha-synuclein aggregation are known, but treatments only manage symptoms.
3. **Huntington’s Disease** – Caused by CAG trinucleotide repeats in the HTT gene, leading to mutant huntingtin protein accumulation. No cure exists.
4. **Amyotrophic Lateral Sclerosis (ALS)** – Mechanisms involve TDP-43 protein aggregation, oxidative stress, and glutamate toxicity, but treatments are very limited.
5. **Prion Diseases (e.g., Creutzfeldt-Jakob Disease)** – Misfolded prion proteins propagate neurodegeneration, but no cure exists.

### **Genetic & Metabolic Disorders**
6. **Cystic Fibrosis** – Caused by CFTR gene mutations, leading to mucus buildup. Some modulator therapies help but do not cure.
7. **Duchenne Muscular Dystrophy (DMD)** – Dystrophin gene mutations cause muscle degeneration. Gene therapies are emerging but not yet curative.
8. **Progeria (Hutchinson-Gilford Syndrome)** – Caused by LMNA gene mutation leading to premature aging; no cure.
9. **Tay-Sachs Disease** – Hexosaminidase A deficiency causes GM2 ganglioside accumulation; fatal with no cure.
10. **Rett Syndrome** – MECP2 gene mutation disrupts neurodevelopment; treatments are symptomatic.

### **Autoimmune & Inflammatory Diseases**
11. **Type 1 Diabetes** – Autoimmune destruction of pancreatic beta cells; insulin therapy manages but does not cure.
12. **Multiple Sclerosis (MS)** – Autoimmune attack on myelin; treatments slow progression but do not reverse damage.
13. **Systemic Lupus Erythematosus (SLE)** – Autoantibodies cause systemic damage; no cure, only symptom management.

### **Infectious Diseases (where vaccines or treatments are lacking)**
14. **HIV/AIDS** – Mechanism (HIV attacking CD4+ T-cells) is well understood, but no cure exists (only antiretroviral suppression).
15. **Herpes Simplex Virus (HSV-1 & HSV-2)** – Establishes latency in neurons; no cure, only antiviral suppression.
16. **Ebola Virus (chronic sequelae)** – Acute infection can be treated with antivirals, but long-term complications lack therapies.

### **Other Conditions**
17. **Fibrodysplasia Ossificans Progressiva (FOP)** – ACVR1 mutation causes abnormal bone formation in soft tissues; no cure.
18. **Friedreich’s Ataxia** – GAA repeat expansion in FXN gene leads to frataxin deficiency; no cure.
19. **Polycystic Kidney Disease (PKD)** – Mutations in PKD1/PKD2 cause cyst formation; treatments only slow progression.
20. **Retinitis Pigmentosa** – Various genetic mutations cause photoreceptor degeneration; no cure for most forms.

Would you like a more detailed breakdown of any of these?
 
Now the other way—disease with treatments but with no known mechanism.

Deep seek


Certainly! There are several diseases for which effective treatments or cures exist, but the exact underlying mechanisms remain unclear or only partially understood. Here’s a list of notable examples:

### **1. Lithium for Bipolar Disorder**
- **Treatment:** Lithium salts are highly effective in stabilizing mood in bipolar disorder.
- **Unknown Mechanism:** The exact neurobiological pathways (e.g., effects on neurotransmitters, neuroprotection, or intracellular signaling) are still not fully understood.

### **2. Electroconvulsive Therapy (ECT) for Severe Depression**
- **Treatment:** ECT is one of the most effective treatments for treatment-resistant depression.
- **Unknown Mechanism:** Why inducing controlled seizures alleviates depression remains unclear, though neurogenesis and neurotransmitter modulation are hypothesized.

### **3. Acetazolamide for Periodic Paralysis**
- **Treatment:** Acetazolamide can prevent attacks in some forms of periodic paralysis.
- **Unknown Mechanism:** The link between carbonic anhydrase inhibition and ion channel stabilization in muscle cells is not fully explained.

### **4. Levodopa for Parkinson’s Disease**
- **Treatment:** Levodopa (L-DOPA) effectively replenishes dopamine and relieves symptoms.
- **Unknown Mechanism:** While dopamine deficiency is known, why dopaminergic neurons degenerate in the first place remains unclear, and long-term treatment complications (e.g., dyskinesias) are not fully understood.

### **5. Colchicine for Familial Mediterranean Fever (FMF)**
- **Treatment:** Colchicine prevents inflammatory attacks in FMF.
- **Unknown Mechanism:** The exact anti-inflammatory mechanism in FMF (a genetic autoinflammatory disorder) is not completely elucidated.

### **6. Intravenous Immunoglobulin (IVIG) for Autoimmune Disorders (e.g., Guillain-Barré Syndrome, Kawasaki Disease)**
- **Treatment:** IVIG is highly effective in modulating immune responses.
- **Unknown Mechanism:** The precise immunomodulatory mechanisms (e.g., Fc receptor blockade, anti-idiotypic effects) remain debated.

### **7. Doxycycline for Filariasis (Elephantiasis)**
- **Treatment:** Doxycycline kills Wolbachia bacteria, which are symbiotic with filarial worms, reducing infection severity.
- **Unknown Mechanism:** Why Wolbachia is essential for the parasite’s survival is not fully understood.

### **8. Propranolol for Infantile Hemangiomas**
- **Treatment:** Propranolol induces regression of these vascular tumors.
- **Unknown Mechanism:** The exact vasoconstrictive, antiangiogenic, or apoptotic effects on hemangioma cells are unclear.

### **9. Methotrexate for Rheumatoid Arthritis (RA) and Ectopic Pregnancy**
- **Treatment:** Methotrexate is a first-line disease-modifying antirheumatic drug (DMARD) and can terminate ectopic pregnancies.
- **Unknown Mechanism:** Beyond folate antagonism, its immunomodulatory effects in RA and selective action on trophoblastic cells are not fully explained.

### **10. Rituximab for Neuromyelitis Optica (NMO)**
- **Treatment:** Rituximab (anti-CD20) depletes B cells and reduces NMO relapses.
- **Unknown Mechanism:** The exact role of B cells and autoantibodies (e.g., anti-AQP4) in NMO pathogenesis is still being investigated.

### **11. Ketamine for Treatment-Resistant Depression**
- **Treatment:** Rapid antidepressant effects via NMDA receptor antagonism.
- **Unknown Mechanism:** Why a single dose can have prolonged antidepressant effects is unclear; synaptic plasticity and mTOR signaling may be involved.

### **12. Allopurinol for Gout**
- **Treatment:** Allopurinol inhibits xanthine oxidase, reducing uric acid production.
- **Unknown Mechanism:** Why some individuals develop urate crystal deposition (gout) while others with similar uric acid levels do not remains unclear.

### **13. Penicillin for Syphilis**
- **Treatment:** Penicillin remains highly effective.
- **Unknown Mechanism:** The exact reasons for disease progression (e.g., tertiary syphilis) in untreated cases are not fully understood.

### **14. Zinc for Wilson’s Disease**
- **Treatment:** Zinc blocks copper absorption, helping manage this genetic disorder.
- **Unknown Mechanism:** The full pathophysiology of copper toxicity in various tissues is still being studied.

### **15. Baclofen for Alcohol Use Disorder (Off-Label in Some Countries)**
- **Treatment:** Reduces cravings and relapse in some patients.
- **Unknown Mechanism:** GABA-B receptor modulation’s role in addiction is not fully mapped.

### **Conclusion**
Many treatments were discovered empirically before their mechanisms were understood. Ongoing research continues to unravel the biological pathways involved in these diseases. Would you like a deeper dive into any specific one?


Same query Chat GPT. This one is bad—lists CFS!!

Here’s a list of diseases where effective treatments or cures exist, but the exact underlying mechanism of the disease remains unclear:


Neurological & Psychiatric Disorders:

1. Schizophrenia – Antipsychotics can manage symptoms, but the precise cause is unknown; theories involve dopamine dysfunction, genetics, and environmental factors.

2. Major depressive disorder (MDD) – Antidepressants (SSRIs, SNRIs) are effective for many, but the exact cause of depression is still debated (chemical imbalance, inflammation, neuroplasticity).

3. Migraine – Triptans and CGRP inhibitors provide relief, but the fundamental cause of migraines (vascular vs. neurological) is still unclear.

4. Epilepsy (some forms) – Anti-seizure medications help control symptoms, but the cause is unknown in many cases.

5. Narcolepsy (Type 2 and idiopathic hypersomnia) – Stimulants and orexin-targeting treatments exist, but the root cause is unclear in some cases.


Autoimmune & Inflammatory Diseases:

6. Rheumatoid arthritis (RA) – Immunosuppressants (biologics, DMARDs) help, but the exact trigger for autoimmunity remains unknown.

7. Psoriasis – Biologics targeting IL-17 and TNF-alpha treat symptoms, but the root cause is unclear.

8. Multiple sclerosis (MS) – Immunomodulators slow progression, but why the immune system attacks myelin is not fully understood.

9. Ulcerative colitis & Crohn’s disease – Biologic drugs manage inflammation, but the precise cause is unclear (gut microbiome, immune dysfunction).


Infectious Diseases with Unclear Pathogenesis:

10. Kawasaki disease – Treated with IVIG and aspirin, but its cause (potential viral/bacterial trigger) remains unknown.

11. Long COVID – Some treatments (rehabilitation, symptom management) help, but the mechanism behind persistent symptoms is debated.


Chronic Conditions & Metabolic Disorders:

12. Essential hypertension – Medications control blood pressure, but the root cause in most cases is unknown.

13. Idiopathic intracranial hypertension (IIH) – Treatments like acetazolamide reduce pressure, but the cause of increased CSF pressure is unclear.

14. Fibromyalgia – Pain medications and lifestyle changes help, but the underlying cause is not well understood.

15. Chronic fatigue syndrome (ME/CFS) – Some symptom management exists, but the mechanism is unknown.


These diseases have effective treatments but lack a fully understood pathogenesis. In some cases, the treatments were discovered by trial and error rather than by targeting the underlying cause.
 
Last edited:
Well that's 21 disease out of maybe five thousand in the textbooks!

I don't see the point of using these as examples. Neurodegenerative diseases do not have known mechanisms by and large. Nobody knows how Parkinson's works. And so on.

For the autoimmune diseases we know a number of things about the processes involved but there are major gaps. We do not know where 'disease memory' lies in the immune system for either MS or lupus. And that is why we have very effective treatments that do not cure.

ME/CFS must be a much easier target than any of these because there is no known permanent damage. The first stage may well be, like lupus and MS, to develop treatments that keep people well without permanent cure. There may still be a problem understanding disease memory in the same way.

But unless mechanism is understood, the chances of throwing drugs at the disease without knowing what is going on being much use is surely infinitesimal. For a start any powerful drug is just as likely to make people much worse as to make them better. And if you take any one drug and any one disease at random my guess would be that the chances that the drug will cure that disease are less than one in a million.
 
I'm not sure what your argument/rationale is for posting this? Is it just general doomerism? Or is it about whether the Norwegian approach vs finding drug targets first is better?

Because I do not see why there should be a binary here. It is perfectly possible to believe the Daratumumab trial is a good thing and hope it succeeds while also recognising that we need the basic science to increase our odds of a successful trial manyfold.

But this comes off quite doomerish at first glance, and certainly would be read that way by non members who haven't read the back and forth in the members only thread that seens to have inspired this.
 
Jaybee00 said:
Posting this for those who believe it will be easy to find a cure for MECFS once a mechanism is found.
Click to expand...
And who has claimed that? And are you attempting to argue that we shouldn't try to find out what the mechanism(s) might be of ME/CFS? If so, I don't understand that at all. There are multiple benefits from discovering that kind of information.
 
Jaybee00 said:
What do you mean by disease memory?
Click to expand...

It's a term often use in discussing autoimmune disease persistence. The question is why the process keeps on going and particularly why it keeps on going despite major remissions in the short term with treatment.

Pretty much everyone with an autoimmune disease is born without autoimmunity. It comes along later and in most cases stays. There are a few odd examples where it spontaneously goes away. Despite having treatments that can make people completely well by removing cellular agents - like B cells - in most cases the disease 'remembers' to come back. For immune thrombocytopenia that is quite often not the case - there is long term cure - but we don't know why.

Theories for disease memory for RA and lupus include it being held in memory B cells, plasma cells, or expanded T cell clones.
 
V.R.T. said:
Because I do not see why there should be a binary here. It is perfectly possible to believe the Daratumumab trial is a good thing and hope it succeeds while also recognising that we need the basic science to increase our odds of a successful trial manyfold.
Click to expand...

I don’t disagree with this and I don’t mean to seem doomerish.

BUT if MECFS turns out not to be immune mediated and new small molecules need to developed, then I think that line of treatment will be a long way away. This is only my opinion so take that with a grain of salt.

ETA.

By contrast, I think I am one of the most optimistic people on here regarding treatment with Daratumumab.
 
Jaybee00 said:
I don’t disagree with this and I don’t mean to seem doomerish.

BUT if MECFS turns out not to be immune mediated and new small molecules need to developed, then I think that line of treatment will be a long way away. This is only my opinion so take that with a grain of salt.

ETA.

By contrast, I think I am one of the most optimistic people on here regarding treatment with Daratumumab.
Click to expand...

That is what I had heard regarding new drugs, but then I had an exchange with Jonathan last year where he laid out a 'reasonable best case scenario' of how a finding in DecodeME could lead to treatment.

https://www.s4me.info/threads/specu...-me-cfs-and-decodeme.34003/page-4#post-541775

But perhaps Jonathan was talking about biologics only. And of course he was just speculating at my prompting, we shouldn't treat it like a prognostication.

Or perhaps this is only in a scenario in which the disease is immune mediated. Which begs the question what kind of disease would it be if it were not?

I confess I know very little about this stuff really, only what I glean from conversations on here.

I am hopeful about Dara but I wont get excited until they've done a positive phase 2.
 
I'm optimistic about finding a treatment or cure, because I had temporary full remissions from three unrelated molecules: cuminaldehyde, prednisone, and T2 (3-5 diiodothyronine). That's without exhaustive testing of substances, so it's not that difficult to encounter molecules that can switch this disease state off. If it isn't easy to find a treatment that switches us and keeps us in the non-ME state, finding a somewhat reliable (works for many PWME) treatment would help identify the mechanism.
 
Jaybee00 said:
See here

https://www.s4me.info/threads/rational-hope-of-treatment.42417/page-3
Click to expand...
Right, so what Jo actually said is
Jonathan Edwards said:
Once we know what we are trying to do, not just in terms of which cell but what the altered dynamics are likely to be devising the right treatment should be easy.
Click to expand...
not
Jaybee00 said:
it will be easy to find a cure for MECFS once a mechanism is found
Click to expand...

I just find it hard to understand your argument against learning more about the condition and instead relying on the lottery of treatments chosen on the basis of what is essentially a hunch.
 
V.R.T. said:
Or perhaps this is only in a scenario in which the disease is immune mediated. Which begs the question what kind of disease would it be if it were not?
Click to expand...

It's worth properly exploring the most likely theories before trying to look for others. What you learn in the process of finding out you're wrong can turn out to be the thing that eventually steers you—or someone else—in the right direction.
 
Kitty said:
It's worth properly exploring the most likely theories before trying to look for others. What you learn in the process of finding out you're wrong can turn out to be the thing that eventually steers you—or someone else—in the right direction.
Click to expand...

I guess I'm just not sure how this disease could NOT involve the immune system in some way. Considering the symptoms and the fact it seems to usually be triggered (and often worsened) by infection.
 
You must log in or register to reply here.
Back
Top Bottom