There has been quite a bit of excitement from the EuroHSP project, investigating a potential candidate drug for SPG4. This work develops on from work recently partially funded by the HSP Support Group. The drugs target is recovering levels of spastin in people with SPG4. There are more details here: https://www.eurohsp.eu/eurospg4
I decided I would have a look and see what else I could find which has been going on recently. I found three different studies looking at gene therapy treatment for HSP, and an article summarising the non-pharmacological treatments for HSP.
Non-pharmacological HSP Treatments
This is the type of article I like. A team in Italy present a review of the different non-medicinal treatments for HSP, and I summarise the article in this post. My overall conclusion is that there are not many papers reporting the benefits of the different types of treatment that people with HSP use.
You can read the full article here: Macorra et al: https://link.springer.com/article/10.1007/s10072-023-07200-1
They undertook a literature review of relevant articles, and focussed their review on studies which met certain criteria. 117 papers/studies were identified, of which 39 were selected for a more detailed examination. From these 13 studies were included for the review.
Physical therapy
Most studies were uncontrolled, and did not report details of timings and details of the types of therapy tested. However the following is noted:
One study reported Functional Electrical Stimulation (FES) on 11 people with HSP and 11 controls. The FES was reported to improve toe clearance during walking and speed of walking. https://www.neuromodulationjournal.org/article/S1094-7159(13)60046-X/fulltext
Another study reports robotic gait training used over 6 weeks. Whilst the study did not report a change in spasticity, the participants had an improved quality of life. https://content.iospress.com/articles/neurorehabilitation/nre1196
Nine people with HSP took part in a 10 week hydrotherapy programme. This improved step length and walking speed, and other gait changes. https://www.sciencedirect.com/science/article/abs/pii/S0966636214000290?via%3Dihub
One study showed that warming legs up for 30 minutes could decrease spasticity and a parallel study showed that 30-60 minutes of warming could increase walking speeds. https://www.sciencedirect.com/science/article/pii/S1877065716300380?via%3Dihub and https://www.sciencedirect.com/science/article/pii/S1877065717304530?via%3Dihub.
A small study showed that an 8 week intensive physiotherapy programme saw improvements in all parameters measured. https://www.ijmhr.org/ijpr_articles_vol1_03/320.pdf
Surgery
Four people with severe spasticity underwent selective dorsal rhizotomy (SDR) surgery. After a 2 year follow up there was a good reduction in spasticity. Another study identified similar benefits in 2 children with HSP, but not in 2 people who's HSP diagnosis became ALS. https://www.jocn-journal.com/article/S0967-5868(13)00322-6/fulltext and https://link.springer.com/article/10.1007/s00381-016-3122-2.
Non-invasive stimulation
A range of studies report using transcranial magnetic stimulation to treat different neurological and/or similar conditions, including reducing spasticity in Parkinson's. Other types of stimulation are noted,
Transcranial magnetic stimulation of the motor cortex is reported for HSP, with 14 people with HSP getting the stimulation over 5 days. Results showed a reduction in spasticity and an improvement in muscle strength. https://www.hindawi.com/journals/np/2019/7638675/
Another similar study of 8 people with HSP showed a reduction in spasticity a month after stimulation, but no change in quality of life. https://journals.lww.com/clinicalneurophys/abstract/2023/02000/a_randomized_controlled_trial_of_the_effect_of.13.aspx
A small study looked at transspinal magnetic stimulation in HSP, but didnt assess outcomes on walking speed etc. Another study looked at 15 people, of which 2 had HSP, testing magnetic root stimulation, with some improvement in spasticity.
Lastly, 11 people with HSP had spinal direct current stimulation for short sessions over 5 days. This showed improvements in spasticity and joint movement. https://www.tandfonline.com/doi/full/10.1080/10790268.2018.1543926.
Gene Therapy
Gene Therapy for SPG50
In the USA one team are working on a gene therapy treatment for SPG50. Their trial tests this in mice, showing some positive results, and testing the safety in a range of animals. They suggest that this approach could proceed to further trials. SPG50 is a childhood onset type of HSP, with additional symptoms beyond spasticity, making it a 'complex' form. There are two articles in the same journal about this:
Chen, et al: https://www.jci.org/articles/view/164575
Brent and Deng: https://www.jci.org/articles/view/170226
Gene Therapy for SPG56
Similarly, another team are working on a gene therapy treatment for SPG56. This research appears to be at an earlier stage, as the announcement I saw reported a contract for two parties to collaborate on this. SPG56 is also a childhood onset type of HSP, with additional symptoms beyond spasticity for some.
You can read more about the wider project here: https://ourmoonsmission.org/
Gene Therapy for SPG61
Finally, another gene therapy target has been identified by a team in Korea. This article reports that the gene ARL6IP1 could be a good gene therapy target for HSP. A quick bit of searching identifies that this gene is associated with SPG61.