Muddled Thoughts on a Cure

I’ve never expected a cure for the SCA3 disease in my lifetime. Nevertheless, I’ve been thinking about it recently, especially in light of citalopram looking promising and some upcoming clinical trials.

What are we talking about?

Cerebellar degeneration. This is the fundamental issue with having SCA that causes external symptoms of ataxia and other maladies. When we talk about curing or modifying the disease, we are only talking about stopping or slowing the cerebellar degeneration, not regenerating the cerebellum or fixing the external symptoms.

Cerebellar stasis. This is my own term, meaning that someone with SCA, with symptoms, who has been “cured” will only initially achieve this: the cerebellar degeneration might stop or slow, but a “cure” won’t help with cerebellar regeneration.

Since SCA is a genetic disease, a “cure” can only prevent the toxic protein, which results from bad genes, from being created or doing harm. The disease is not actually cured, but the effects of the disease are masked, or weakened, and only fractionally and thus temporarily.

If cerebellar degeneration stops or slows, what happens to one’s symptoms? I don’t think they will go away. I muse more about this ahead.

Cerebellar regeneration. We must also consider the possibility of rebuilding a degenerated cerebellum. Science tells us now that regenerating neurons is impossible. The need/desire for this will be strictly based on how much degeneration has occurred. Also, I assume any regeneration would be temporary, until degeneration again gets the upper hand.

Donor stem cells (SCA-free) injected into the brain could help here (temporarily, perhaps in the future; a bit science-fictiony at the moment, considering that neurons cannot be replaced; or can they? Or can they really?). The older, defective cells could still end up dominating. Who knows? Maybe an injection of embryonic stem cells into the brain will work wonders.

Physical rehabilitation / physical regeneration (e.g., of eyes, limbs, tongue for speech; bladder, esophagus). Let’s say that achieving cerebellar stasis is the primary end-goal. Then depending on the severity of your symptoms (if any), your primary option will be physical rehabilitation of some sort, possibly including stem cell injections to help rebuild the physical degeneration (i.e., external symptoms) that have occurred.

Stem cell treatments?

For decades, I’ve wished people would shut up about ataxia and stem cells! In the last few decades, the treatment talked about and pushed was getting stem cell injections into the limbs with an obliviousness to the fact that treating symptoms won’t affect the underlying brain disease. That hasn’t stopped a lot of people.

Recently, there have been successful human experiments (unrelated to ataxia) with injecting stem cells into the brain. This could get a step closer to being useful, but in the case of ataxia without a “cure,” this won’t stop continued degeneration.

There also has been some SCA3-specific experimentation around using stem cells implanted in the brains of mice.

This can’t prevent the disease but can only possibly repair or workaround some of the damage that is done. Waiting for repairable damage and then repairing it temporarily is hardly a solution, in my book.

In other words, stem cells can’t eliminate a genetic disease, before or after symptoms have started. Stem cells injected into the brain will work best for someone who’s had a recent external event damage their brain, such as a stroke—not progressive damage to the brain and body over a few decades, especially when the defective cells are in the brain itself.

From 2017-10-05: “In a First, Gene Therapy Halts a Fatal Brain Disease“:

  • This is a report on a human trial, not an available therapy.
  • Defect-free stem cells are injected into the bone marrow. After a year or so, new cells make it to the brain, differentiate as glial cells, and help protect the existing neurons (which remain with the defect). This sounds like a slower (slow motion, really), less risky alternative to brain injections (ICBI).
  • Best case is that neuronal damage is halted but not repaired. The defective neurons might still get the upper hand over time.
  • Study details.

The need for rehabilitation

A cure might stop or slow the disease (i.e., the cerebellar degeneration), but it won’t necessarily fix the external symptoms. Cures for the ataxia diseases will mostly benefit those without symptoms. The least benefit will go to those who have had symptoms the longest.

Someone with SCA for (e.g.) 20 years has been declining for 20 years, with issues compounding to the point where they are probably only distantly related to the cerebellum; kicked off by the degenerating cerebellum, yes, but now perhaps distantly related to that root cause. Someone who hasn’t walked for 10 years isn’t going to suddenly jump out of their wheelchair after a cure or modification is applied to them. If they spent 10 or 20 years getting into a wheelchair, it’s going to take quite some time and effort to get out (if possible at all), even if the damage to the brain is fixed or stopped completely.

For example, does ataxia cause scoliosis? No, not pathologically, but nearly everyone with late-stage ataxia might have scoliosis because they’ve had bad posture for decades. Will a cure for ataxia cure scoliosis? Absolutely not. It won’t even scratch that surface.

Some support groups teach that SCA is not a disease. If you refuse to think you have a disease, that might warp your expectations of what a cure or modification will offer. A cure or modification won’t outright fix your symptoms, especially if they are advanced, possibly leaving your expectations unfulfilled—a cure or modification might only pave the way for rehabilitation to be remotely possible.

More of what I expect

SCA results in degradations that multiply and never improve. That bears emphasizing. Even if you do everything right, take supplements, exercise, and eat properly, even if any or all of these things help, none will bring your condition back to the way it was at a prior time. The best you can hope for is to slow the degradation. The nebulousness of that is so high, even those with the disease have widely varying interpretations and expectations of what’s going on.

For example, I have taken coenzyme Q10 for over 15 years. Does it help me? That is unanswerable; the answer is unknowable. In all those years, months, and days of taking it, I have no evidence that it’s benefiting me. On a day-to-day basis, it has no effect, yet I continue to take it. I will take to the grave not knowing whether it has slowed the progression of SCA3. Even if I stopped taking it, I wouldn’t know if not stopping would have been more beneficial. Whether or not I take CoQ10, the degradations caused by having SCA3 will continue.

Today, nothing makes improvements; things can only slow down how fast the symptoms worsen. Treatments and modifications will be like that, as well. Certain years-long symptoms might begin to recede if there’s no impetus for them to get worse. In that case, physical therapy might accelerate the improvements.

It could be hard to fully appreciate “not getting as worse as fast” as the best a cure or modification might have to offer. And what to expect is unknowable despite what anyone might say otherwise. Firstly, specific cerebellar degeneration (and for that matter: regeneration) cannot be directly correlated to symptoms; external symptoms are a manifestation of the cerebellar disease but not an exact reflection. Secondly, as an example, I tend to think that nystagmus comes from diplopia, which comes from ophthalmoparesis, which comes from SCA3; if you have nystagmus and ameliorate the SCA3, what happens to the ophthalmoparesis, the diplopia, and the nystagmus? No one can know because it’s never happened before. Physical therapy might help, but I don’t have high hopes for ever walking off into the sunset.

Symptomatic relief could be quick (and temporary), taking effect (and stopping effect) instantaneously or in a few minutes to a few days. Modifying the disease could take weeks, months, or years.

 

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