You're probably right to look at gene therapies.  This might be the best hope of actually getting something curative.  Of course, NINDS has it right that nothing is established or proven to work.  So if giving up is not an option, then you're exactly right to look at something unproven and highly experimental. 

The problem with gene therapies is that folks aren't very good at delivering enough transgene to enough cells.  There is a tendency to sweep this issue under the rug, jump straight into efficacy testing, and then cherry-pick until Professor Bonferroni turns in his grave.  

So you'll need to approach this kind of research with a critical mindset and check your wishful thinking at the door.  Do the advocates of the therapy acknowledge that their one key problem is delivery efficiency?  Do they attempt to measure it in a relevant model or even a patient?  Or do they try to ignore the issue and hope you don't notice? 

Such a mindset will hopefully help you to separate the many people whose primary motivation is to win the next grant, from those who are willing to put the next grant at risk in order to ask difficult scientific questions to actually learn about their treatment. 

Good Luck.

Dear John,

many thanks for your honest answer.

I have no illusions, and I know the disorders and problems of the medical sciences and researches. For example, from here:  http://www.medpagetoday.com/Cardiology/CardioBrief/55722

"The science of nutrition is a disaster. ..."

Aaron P. Mitchell, Ethan M. Basch, Stacie B. Dusetzina:

Financial Relationships With Industry Among National Comprehensive Cancer Network Guideline Authors

JAMA Oncology, Published online August 25, 2016. doi:10.1001/jamaoncol.2016.2710

http://oncology.jamanetwork.com/article.aspx?articleid=2546172

https://www.researchgate.net/publication/306932243

And from the comment to this article, by Stephen B. Strum:

The Business of Medicine: Conflicts of Interest Are the Norm (Posted on August 26, 2016):

 "I have been involved in cancer medicine for 53 years and it was clear ... In my lifetime I have seen medicine devolve from a profession to a business. I think we should replace the MD degree with a Business of Medicine degree."

From here: http://www.bmj.com/content/351/bmj.h5414/rr

"... Science tells us what’s true, while philosophy tells us what’s truly useful. ..."

But nobody can tell what’s truly useful and nobody can tell what’s truly healthy, because the science don’t tells the truth.

One very good example - the "science" of salt:

 Sodium-Induced Disorder Syndrome. Where have all the sciences gone?

BMJ Online (13 April 2016)

https://www.researchgate.net/publication/301297340

http://www.bmj.com/content/351/bmj.h4962/rr-45

Article Sodium-Induced Disorder Syndrome. Where have all the sciences gone?

Article Financial Relationships With Industry Among National Compreh...

Although I agree with most of the comments from John I would stay on a positive view. I know the disease and how devastating is for the cihldren affected. I also worked for a period on a gene therapy for SMA that did not advance further for lack of funding.

At the link below you can get an updated oveview on how is going the research in the field. You will see there are 7 projects in clinical stage and many more in preclinical research. DIfferent approches are being followed e.g. antisense oligonucleotides, gene therapy, small molecules. Some preliminary findings are encouraging but much more time is needed to see at least one of these reaching the market and be available for patients.

The second link refers to the largest European Registry, the Treat-NMD a non for profit organization dedicated to neuromuscular disorders including SMA. Maybe getting in touch with them may offer the chance to be included in some clinical study. As there is no therapy available and the clinical evolution of the disease is irreversibly progressive at least is a chance.

Best wishes and good luck

http://www.curesma.org/research/latest-advances/

http://www.treat-nmd.eu/

Dear Marco,

thank You very much. I found Hungarian section.

http://www.treat-nmd.eu/registry/307/

Dear Zoltan,

Please check out the work of Brian Kaspar, Jerry Mendell and colleagues with AveXis:

http://investors.avexis.com/phoenix.zhtml?c=254285&p=irol-newsArticle&ID=2166123

I'm not sure if this is the sort of thing you're enquiring about

Kind regards,

Simon

Dear Zoltan,

There is now a highly successful treatment for type I SMA: Nusinersen - Biogen/Ionis stopped the phase III trial early as all endpoints were met at an interim analyis point and Biogen has just finished submitting a NDA to the FDA.Nusinersen is also in trials for type II and III SMA (as I understand the disease, your patient cannot have type I as median time to death for type I is 8-10 months after birth).

Biogen is in the process of opening an expanded access program

https://www.biogen.com/en_us/research-pipeline/how-to-request-access.html#nusinersen-expanded-access-program

to make the drug available before approval.

Dear Petra and Simon,

Thanks for the answers.

Really, the type 1 is unbelieveable. (This is the Hungarian reality in health services.) Within some weeks will be clarified the new and (perhaps) correct diagnose.

Note: The little girl (Narcisz) is not my patient (and I am not a medical doctor). I look for the possible therapies for a friend's of mine request.

Dear Zoltan,

I'm not a medical doctor either, just a biomedical researcher with an interest in the oligonucleotide therapeutics field.

As M. Sardina suggested, please do encourage the family to get in contact with a patient support group - this can be incredibly helpful for them, as other parents will know how to find&access grants for support (wheelchairs and so on), what sort of physiotherapy can be helpful and just act as general emotional support.

Here are some links for Europe and Hungary in particular:

http://www.sma-europe.eu/

http://www.rirosz.hu/ (not sure about this one as I don't read hungarian, but it is meant to be a rare disease organisation)

Also, from en.care-nmd.eu/userfiles/file/events/.../6_3karcagi_hungarian_registry.pdf

Budapest Neuromuscular Center was launched in 2012. The

Center aims to treat Hungarian neuromuscular patients

according to European and international best practices. It

follows the international guidelines published in Lancet

Neurology in 2010. Quality of life and life expectancy of

DMD (and other NMD) young patients should be improved.

• The first Hungarian Neuromuscular Centre is lead by the 2nd

Pediatric Clinic of Semmelweis Medical Unversity.

• The cooperating institutes are: National Institute of

Environmental Health (genetic diganosis), National Institute

of Child Health (genetic counselling), the Pediatric

Rehabilitation Department of Szent János Hospital

(rehabilitation), Pulmonology Institute in Törökbálint, Misko

Foundation, Duchenne Foundation „Gyógyító Jószándék”,

Hungarian SMA Children’s Foundation and RIROSZ.

If it is possible to get Narcisz' medical care transferred to one of those centres, that could be very positive for her.

Best wishes for her health

http://www.rirosz.hu/

en.care-nmd.eu/userfiles/file/events/.../6_3karcagi_hungarian_registry.pdf

I say thank you for it Petra,

some of them is familiar already.

Dear Zoltan,

See attached.

BW, Simon

Thank you for it, Simon!

https://www.msn.com/en-us/money/healthcare/a-dollar2-million-drug-is-about-to-hit-the-market/ar-AAB1eN9?li=BBnb7Kz&utm_source=fark&utm_medium=website&utm_content=link&ICID=ref_fark

A $2 million drug is about to hit the market (Novartis AG)

https://index.hu/techtud/2019/05/08/600_millio_forintba_kerul_a_legdragabb_gyogyszer/

580 millió forintba kerül a világ legdrágább gyógyszere

https://www.wsj.com/articles/a-2-million-drug-is-about-to-hit-the-market-11557221401

Zoltan, thank you for sharing. It is good to see more options for patients with this devastating disease.

However, there are some issues with Zolgensma that are worth mentioning. There is a problem with AAV antibodies (maternal or acquired) that limits how early a baby can receive the gene therapy (earliest 1 month after birth) or excludes patients from treatment. Perhaps Simon N Waddington could comment on this? Also, as far as I understand, Zolgensma approval will be only for infants younger than 9 months, and there may be some issues with systemically injected AAV crossing the blood brain barrier which is why they are going to intrathecal delivery on older kids. Again, Simon N Waddington would know much more about this.

The accumulated Sprinraza data clearly points to the fact that the earlier you start treating, the better the outcome. Presymptomatic treatment (as soon as possible after birth - ideally identified by screening within a few days of birth) with Sprinraza has been shown to result in near normal development - see NURTURE trial data.

Comparisons between Zolgensma and Sprinraza attempt to use the equivalent trials matched by age and type (ie compare the ENDEAR trial with current Zolgensma data). I would say that you really need to look at the Spinraza NURTURE data as that is the best that can be done with Spinraza and compare with the best that Zolgensma can do (SPR1NT). See this article for a discussion of the finer points:

https://seekingalpha.com/article/4255679-ioniss-spinraza-still-bests-novartiss-zolgensma

Another point that isn't widely discussed is that 15 of the 22 early Zolgensma treated kids are now on Spinraza (sorry numbers off the top of my head and can't seem to find the link, but Novartis have discussed this on an earnings/investor phone call) and that is because they plateaued in their improvement after Zolgensma treatment.

That means that any long-term efficacy may well come from Spinraza... As it stands, there is no long-term data that shows that the gene therapy efficacy will be for life (or at least more than 2 years) as seems to be assumed and the switch to Spinraza by lot's of the kids suggests it is otherwise - don't get me wrong, I'd love for it to be a one-time treatment = cure, but as a scientist I want data.

And the last point to make is that the cost of producing a clinical grade AAV gene therapy is significantly higher than producing an antisense therapy simply due to the complexity involved (we're talking a factor of ~1000x).