Research program update September 2022

Progress with assays and biomarkers

SPG7 research

Gautam Wali

The current SPG7 research project, funded by the SP Foundation (US), has now been completed by Dr Wali and his team in Prof Carolyn Sue’s lab at the Kolling Institute, Sydney University. Using induced pluripotent stem cell-neurons developed from tissue samples of people with SPG7, the team has established a suite of assays that identify disease-associated impairments in patient cells. 

The next step is to use these high-throughput assays to test and screen for drugs that correct the impairments and restore normal function in the SPG7 stem cell-neurons.

The major work of the quarter has been the completion of this project. They will now work on drafting a scientific paper for publication and seeking out funding opportunities for the next phase, drug discovery.

SPG4 biomarker

We are hopeful of Dr Wali being able to validate the blood biomarker compound as a measure of disease progression in SPG4. One of the issues in delaying going to clinical trial is the lack of a definitive marker of disease status over time. Given the slow rate of progression in SPG4, a phase 2 trial needs to be of at least 12 months duration. Over any given 12-month period in people with SPG4, normal disease progression would span a wide range, meaning some people would remain pretty much the same, some would have minor worsening of symptoms and others would experience significant worsening of symptoms in that timeframe.

The challenge in a clinical trial is to accurately gauge the difference over the 12 months, and then compare progression between the group that is being treated and the group receiving dummy medication. The process of obtaining suitable blood samples for this biomarker validation study is underway.

Developments in gene therapies

We are keenly watching developments in therapies for children with HSP. In the June update, there was an article on parallel drug and gene therapy development in SPG56 that is underway in Queensland, with the drug development pathway being investigated at Griffith University and the gene therapy pathway proceeding at the University of Queensland.

In March in Toronto, Canada, a four-year-old boy with SPG50 underwent gene therapy, a procedure where a healthy copy of the AP4M1 gene was injected into the boy’s spinal fluid. The procedure proved safe, with effectiveness to be assessed over the coming months.

Two families in the US, each with a child who has a sporadic, complicated form of SPG4, have teamed up to initiate a gene therapy program in which the treatments are currently being tested on SPG4-affected mice.

Also in the US, we have reported previously on the development of a candidate drug for motor neuron disease (MND) at Northwestern University in Chicago that also holds potential for treating HSP. Recently it has been reported that studies have found that the compound, known as NU-9, lengthened the axons of diseased neurons in mice with motor neuron disease. The treatment was found to be more effective than existing drugs for the disease, but with enhanced effect when given in combination with the existing drugs. Animal studies are continuing with the prospect of clinical trials early next year.

You can read articles on these developments in the Foundation News section on the website homepage.


  1. Do researchers try medications for ALS on people with HSP? Meds like Relyvrio with few side effects? I think most of us would be willing to try any medication to slow the progression of this disease.

    1. Editor’s Note: There is no easy way for researchers to effectively and legally “try” medications on people. The process of establishing sufficient evidence to get regulatory approval to conduct a clinical trial for a drug or other therapy is long, difficult and expensive. Then there is the clinical trial itself that is equally as challenging. Individuals can ask their doctor or specialist about trying a particular drug. If the doctor determines that it is okay to try a particular drug, they can write what is known as an ‘off label’ prescription, meaning treatment for a medical condition that the drug is not approved to treat. An example of this is dalfampridine (Ampyra or Fampyra) a drug used to treat symptoms of multiple sclerosis that some people with HSP have found helpful.

  2. Dear Editor HSP research foundation
    Please make a try to start investigating a drug for SPG84, because I have two children with this type of HSP.

  3. Is there any drug that can increase noggin or other bmp inhibitor drugs but bmp 2 signaling inhibitor can rescue nipa1 SPG6.

    1. Editor’s note: We have no researchers working in this area to answer your question. Suggest you correspond directly with the Reid lab at Cambridge University in the UK where they have been studying BMP signalling and inhibition in HSP for some years.

  4. My doctor told me that the current treatment plan for HSP is to treat symptoms, not slow or stop the disease. I don’t understand this. MS and ALS both have medications that help to slow disease progression. Is HSP newer or not understood as well as these diseases? The ALS site currently shows 160 clinical trials recruiting participants on their website with over 10 interventional medications being investigated, I am not seeing any recruiting studies for investigational medications for HSP on this site or through searches. Can you direct me to these? Does ALS get more money for research than our disease? I know ALS is much more severe, but I thought HSP was more prevalent.

    1. Editor’s note: MS (36 per 100,000 population) is 5 times more prevalent than HSP (3 – 8 range per 100,000 population), while ALS has roughly the same prevalence range as HSP. Both MS and ALS have received much greater attention in research and funding than HSP over time and continue to do so (presumably because MS is much more common and ALS much more severe). Priorities are dictated between a combination of government policies, pharmaceutical industry decisions and the ability of individual conditions to get noticed. HSP sits in amongst roughly 7,000 rare diseases currently recognised, at least 80% of which have a genetic basis, fighting for exposure, attention, awareness and, ultimately, funding as they all do. Because 8 – 10% of the total population is impacted by a rare disease, at least at some point in their lives, if not chronically, governments are now starting to recognise the overall impact, resulting in policy and program frameworks to address this huge unmet need. In the meantime, as you point out, MS and ALS have clinical trials and established or emerging treatments, but HSP and 95% of the 7,000 rare diseases do not.

  5. Can you provide an update on the drug Noscapine that was being developed/researched? I haven’t seen an update in a while.

    1. Editor’s note: This is an example of a candidate drug, in this case for SPG4 type HSP, waiting to be tested in a clinical trial, for which funding has not been gained. There are some technical challenges – it would be great if there was a definitive marker and measure of disease status suitable for use in a clinical trial, and pre-clinical investigations are advancing on this, but again, more funding would greatly help accelerate this as well. Short of receiving some unexpected windfall, we do what we can to attract attention, raise awareness, apply for grant funding – and patiently wait in line with the other 7,000 rare diseases for our turn.

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