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Neurological & Neuromuscular

Hereditary Spastic Paraplegia (HSP) Clinical Trials

Also called HSP, Familial Spastic Paraplegia, Strumpell-Lorrain Disease

Hereditary Spastic Paraplegia is a heterogeneous group of genetic neurological disorders unified by selective degeneration of the distal axons of corticospinal motor neurons. Over 80 genetic forms are recognized (SPG1-SPG81), each caused by mutations in different genes encoding proteins involved in various cellular processes: axonal transport, mitochondrial function, membrane trafficking, lipid metabolism, and protein degradation.

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About Hereditary Spastic Paraplegia

Hereditary Spastic Paraplegia is a heterogeneous group of genetic neurological disorders unified by selective degeneration of the distal axons of corticospinal motor neurons. Over 80 genetic forms are recognized (SPG1-SPG81), each caused by mutations in different genes encoding proteins involved in various cellular processes: axonal transport, mitochondrial function, membrane trafficking, lipid metabolism, and protein degradation. The common pathological feature is degeneration of the longest corticospinal tract axons, affecting the ability to control leg movement.

HSP manifests with progressive lower extremity spasticity, weakness, and difficulty walking. The spasticity develops insidiously over months to years, with progressive stiffness of leg muscles and hyperreflexia. Some patients show relatively pure HSP with only lower extremity involvement, while others (complex HSP) have associated features including cognitive impairment, seizures, ataxia, peripheral neuropathy, vision loss, or hearing loss depending on the genetic subtype. Disease progression varies widely by subtype: some forms have static or very slowly progressive disease allowing lifelong ambulation, while others show rapidly progressive paraplegia requiring wheelchair use within years of onset. Genetic heterogeneity means that even within the same family, disease expression can vary.

Common Symptoms of Hereditary Spastic Paraplegia

Recognizing the signs of Hereditary Spastic Paraplegia early can lead to faster diagnosis and better outcomes. Symptoms may vary in severity from person to person. If you or a loved one are experiencing any of the following, consider speaking with a specialist.

  • Progressive spasticity and muscle tone increase in legs
  • Weakness of lower extremities affecting gait and walking
  • Hyperreflexia and increased deep tendon reflexes
  • Extensor plantar responses
  • Progressive loss of ambulation in severe forms
  • Pain and muscle cramps

Who Hereditary Spastic Paraplegia Affects

Age of onset varies widely by genetic subtype, ranging from early childhood to adulthood. Some forms present in early childhood; others in late adulthood.

Affects males and females, with gender bias depending on inheritance pattern (X-linked forms more severe in males). Multiple inheritance patterns: autosomal dominant, autosomal recessive, and X-linked. Over 80 genetic subtypes with variable ethnic distribution.

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Genetic Testing

Genetic testing can confirm a diagnosis, guide treatment decisions, and identify family members who may be at risk.

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Trusted Hereditary Spastic Paraplegia Resources

Reputable organizations and medical references for learning more about Hereditary Spastic Paraplegia, including disease registries, foundation resources, and clinical guidelines.

Active Clinical Trials for Hereditary Spastic Paraplegia

Use this Hereditary Spastic Paraplegia clinical trial finder to see the 21 studies recruiting patients and 1 opening soon in the United States and worldwide, with eligibility criteria in plain English. These studies play a critical role in advancing care for neurological & neuromuscular conditions and may offer access to treatments not yet widely available. Each trial below is sourced directly from ClinicalTrials.gov, with eligibility criteria translated into plain English to help patients and caregivers evaluate whether a study may be a fit.

TrialsSite mapPipeline timeline

Note: Trial recruitment statuses on ClinicalTrials.gov may not immediately reflect recent FDA decisions, sponsor announcements, or enrollment changes. Always confirm a trial's current status directly with the study coordinator before making plans.

22 active trials worldwide
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RECRUITINGRecently updatedNCT07798674

TreatHSP Platform: Adaptive Natural History Platform for Ataxias, HSPs, and Spastic Ataxias

Sponsor: Heidelberg University · Horizon Europe

Ataxias, hereditary spastic paraplegias (HSP), and spastic ataxias (collectively referred to as SPAX diseases) are rare neurological conditions that cause progressive problems with walking, balance, coordination, and daily activities. Although many SPAX diseases are caused by spe...

Ages 5 Years+30 locations
Started Jul 2024Updated 4 weeks agoEst. Dec 2035 (~9y 3m)
RECRUITINGRecently updatedNCT06092346

A Natural History Study Seeks to Understand the Clinical, Genomic, Pharmacological, Laboratory, and Dietary Determinates of Pyrimidine and Purine Metabolism Disorders

Sponsor: National Human Genome Research Institute (NHGRI)

Background:

Ages 1 Month – 100 Years1 location
Started Dec 2023Updated 1 month agoEst. Jan 2099 (~72y 3m)
RECRUITINGPHASE1, PHASE2Recently updatedNCT05518188

Melpida: Recombinant Adeno-associated Virus (Serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)

Intervention: MELPIDA

Sponsor: Elpida Therapeutics SPC

MELPIDA is proposed for the treatment of subjects with SPG50 and targets neuronal cells to deliver a fully functional human AP4M1 cDNA copy via intrathecal injection to counter the associated neuronal loss. Outcomes will evaluate the safety and tolerability of a single dose of ME...

Ages 4 Months – 10 Years1 location
Started Feb 2023Updated 2 months agoEst. Oct 2028 (~2 years)
RECRUITINGNAUpdated a few months agoNCT07417943

Neuromodulation to Enhance Motor Function in HSP

Intervention: transcutaneous spinal cord stimulation

Sponsor: Rahul Sachdeva

Hereditary spastic paraplegia (HSP) is a rare neurological condition that causes stiffness, weakness, and difficulty walking due to damage in the nerves that control movement. This study will test whether a noninvasive form of spinal cord stimulation, called transcutaneous spinal...

Ages 18 Years+1 location
Started Apr 2026Updated 5 months agoEst. Dec 2027 (~1y 3m)
RECRUITINGPHASE3Updated a few months agoNCT06692712

Phase 3 Efficacy Study With Concurrent Control of IT MELPIDA in SPG50.Concurrent Controls.

Intervention: MELPIDA

Sponsor: Elpida Therapeutics SPC

Phase 3, open-label study to assess the efficacy and safety of a single lumbar intrathecal administration of MELPIDA in individuals with Hereditary Spastic Paraplegia Type 50 (SPG50).

Ages 4 Months – 72 Months2 locations
Started Apr 2026Updated 5 months agoEst. Feb 2032 (~5y 5m)
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Active trial locations13 cities in the US
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Trial Pipeline

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Data from ClinicalTrials.gov, U.S. National Library of Medicine.
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Related Neurological & Neuromuscular Conditions

Other rare diseases in the neurological & neuromuscular category. Patients with Hereditary Spastic Paraplegia may find relevant research, shared treatment pathways, or overlapping clinical trials among these related conditions.

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