Finding a pathway forward
SPG4 clinical trial
You may remember in previous research updates we talked about roadblocks to moving forward with the clinical drug trial for SPG4. With the expectation that the roadblock due to the COVID pandemic is not permanent, the main impediment to progress is financial, both directly and indirectly. With the sticker price of a phase 1 clinical trial tripling over earlier estimates, the ‘risk’ profile of the initiative shifted substantially. The level and quality of evidence required to proceed to clinical trial also went up commensurately. It is time in the Foundation’s development to have a Scientific Advisory Board (SAB) or equivalent function, independent of the Foundation to advise and guide on investing research funding.
Although a step in the right direction, an SAB is not the perfect vehicle to be making decisions about proceeding to clinical trial. It is a different context with different questions to address than when deciding on the merits of one or more research projects. Neuromuscular diseases NMD as a group came together some years ago and created TACT (Treat-NMD Advisory Committee for Therapeutics):
“Established in 2009, the TREAT-NMD Advisory Committee for Therapeutics (TACT) is a unique multi-disciplinary international group of internationally recognized academic and industry drug development experts as well as representatives of patient foundations and regulatory experts, who meet twice a year to review and provide guidance on the translation and development path of therapeutics programs in rare neuromuscular diseases.”
They are effective and have an excellent track record, with the development of treatments and cures in recent years for Spinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD).
Neurodegenerative diseases NDD, a group that includes the HSPs, could do the same, coming together as a group, with one of the purposes being to establish an advisory committee for therapeutics, as TREAT-NMD have done so successfully.
The Foundation is actively moving forward to get the help that we need in this regard.
SPG7 research
The SPG7 induced pluripotent stem cell (iPSC) project, funded by the SP Foundation (USA), using both olfactory stem cells and iPSC-derived neurons is progressing well. Work is ongoing to more precisely understand the disease mechanism, paving the way for drug discovery. This is the same pathway that was taken with the SPG4 research program that investigated the disease mechanism and produced drug candidates.
Blood biomarker to test Noscapine delivery and action
Over the past year Dr Wali and the team at Kolling Institute (U of Syd) have shown a novel application of a high-throughput assay to measure a pharmacodynamic biomarker using nanomolar protein concentrations appropriate for clinical trials. They have successfully shown the effectiveness of this biomarker in a) brains of mice dosed with noscapine, and b) human blood cells treated with Noscapine in the laboratory dish (in-vitro). This work demonstrates a potential biomarker for the delivery and action of Noscapine in individuals in a clinical trial. This work is now submitted to a scientific journal for review.
Further biomarker development opportunity
The blood biomarker that can identify Noscapine induced biological changes in human blood cells has already been successfully developed and validated as a high throughput assay by Dr Wali, as reported previously https://hspersunite.org.au/research-program-update-september-2021/. This could be described as being at the ‘input’ end of a clinical trial, however at the ‘output’ end, measures of drug treatment effectiveness showing up as improved clinical outcomes e.g. improved mobility, reduced spasticity and so on, could be more precise than the clinical measures currently available.
There is now the opportunity to test the blood biomarker as a measure of HSP disease severity, progression and, potentially, improvement in HSP status as a result of treatment in a clinical trial for SPG4. To do so requires a study with a large sample size with the potential to give definitive results. Suitable human blood samples in sufficient numbers exist in an international biobank, however they are both in limited supply and expensive to make, requiring a convincing application to the biobank for them to be shared for such a study. That process is in progress. Success will give confidence for conducting clinical drug trials for SPG4 a significant boost.
I am happy to be part of your SPG4 trial. I have a long family history of HSP, specifically SPG4.
Editor’s Note: Thank you Tara. When the time comes, there will be blanket communications about the trial, who is eligible, how to register interest and so on. You won’t miss it!
I am happy to be a part of your SPG4 trial.
The research is sounding positive for the moment great we all needed to hear there was an update ,we all will be waiting to see how the Mice go, and the next stage in your Research goes.
And yes I forgot to Mention Dr Wali’s work great with Noscapine if you need someone to try the drug I am ready thanks.
Hiya. I would love to be able to help with this. I have HSP4 as does my daughter. I am 65 and my daughter 34. She has decided to have no family because of this which is heartbreaking. Please continue and do whatever you can. flowers xxx
My husband has SPG7 and we would be very interested in any research trials. Great work !
I already take Noscapine.
been taking it for about 2 years now.
Its working for me, I buy mine overseas.
Was hard to find. I know a few other people that are also taking Noscapine.
I still use a walker and exercise and stretch every day for a good 1/2 hour.
also see a Physio for deep tissue massage. use a massage gun, Tens Machine, AFO sometimes, Night Splints when feet are sore.
Resistance bands for my leg muscles, use some days.
a Pilates Reformer most days.
I still have to work my muscles.
Where do you buy NOSCAPINE, what brand, model, pharmacy, country, if they are pills, capsules or syrup? I would like to test it, seeing that it works for you. What dose do you take??? Kind regards from José Miguel
Hello can you tell me where you buy noscapine？
Is this trial purely for research into the SPG4 gene or can it cover all the people who have different genes? also as I have hsp but not had my gene found yet so would I be eligible for research as it sounds very promising in giving us some hope that there will be some kind of cure or a new medication that will help us greatly to have a better quality of life!
Promising development… looking forward to improved treatment options. Is there any insight on patient qualifying factors in using the med if it moves forward in patient use?
I tried Noscapine a few years ago. I didn’t think it was helpful and I had some type of side effect. I can’t remember what it was so I don’t think it was that bad. I still have a large bottle of the Noscapine. Wondering if I should try it again and at what dosage. There wasn’t much info on that when I took it before. Seemed like people with HSP were just trying it out in whatever dosage they thought would work. If I had some guidance from a doctor or medical study on dosage and possible side effects that would be helpful.
I’m from Mexico, here in Mexico we don’t have a technological advance like this, I would love to be taken into account, I’m so desperate
I would certainly be willing to try the drug. Can it be purchased over the counter?
I have SPG4. My name is Brenda and I am 47 years old. I was diagnosed in 2007. I have a family history of it. I would be very interested in participating in a clinical trial!
Very interested in participating in the trial when time comes
Happy to take part
I have been diagnosed with SPG7, I am very excited about your research and would love to help in the trial.
Editor’s note: Thanks all for your interest. To clarify:
* The first step will probably be the establishment of a registry, hopefully with the opportunity for both neurologists and people with HSP to register interest in trial participation.
* Criteria for inclusion and exclusion will include both medical and geographic considerations.
* The proposed trial is aimed at SPG4.
* Noscapine is available over-the-counter in some countries, mainly in Europe and Asia, while it is not available in many other countries.
* There can be no recommendations or guidelines on the use of the drug until evidence for its safety and effectiveness for HSP is established. This can only be done by clinical trial.
* If the drug is approved for HSP and reaches the market at some point, all the information normally associated with a prescription drug will be available – who can take it and who can’t; when, how and how much to take, as well as any potential risks.
* Whether or not the drug works for other forms of HSP will need to be the subject of a separate clinical trial. Costs and logistics would make the size and scale of a more inclusive trial impossible. Part of this is because of the relatively large numbers with SPG4, whereas with other forms of HSP, different clinical trial designs would be needed due to the much lower numbers of people who could participate.
I will be happy to be part of the trial for SPG4. I have have been genetic tested and willing to go where ever it is needed to do it or any kind of help.
Diagnosed with HSP SPG4. Very interested in participating in the clinical trial
I have been diagnosed with two HSP Markers. SPG4 & SPG7. Let me know if I am eligible for the clinical trial.
Editor’s Note: Probably not technically because you have two forms of HSP, and highly unlikely geographically unless the trial happens to be held within about two hours driving time of where you live. Are you saying that you have genetic test results that are positive for both SPG4 and SPG7? If so, that is almost certainly unique and has never been previously reported. Many researchers would be interested in this. If you are comfortable doing so, please email copies of your genetic test results – images from your phone would be sufficient – and we will share them with researchers after removing identifying information such as name, address and contact information.
I live in the U.S. and about 4 years ago I started taking Noscapine that my wife purchased from a company in Australia because it didn’t have FDA approval in the U.S. as of yet. It started after about 3-4 weeks of taking two tablets a day. The muscles in my legs loosened up and my gait was much better. I didn’t drag my feet as much. When Covid hit I wasn’t able to get it after I ran out around the end of 2020. In 2021 my gait worsened, and my legs were extremely tight even though I could still walk. Things tended to get worse with time. In May of 2022 I was able to get it again. Within 3 weeks I could feel the difference. My gait improved again, and I no longer had the spasticity in my ankles and calves that I felt prior.