Clinical & genetic overlap with Ataxias
Clinical and genetic overlap between the HSPs and Cerebellar Ataxias leads to an intermediary group of Spastic Ataxias, the most striking example of which is SPG7.
The broad spectrum and diversity amongst the HSPs makes the search for effective treatments that much more difficult, with a variety of different disease-causing mechanisms involved in a significant number of potential focus areas (targets) for treatment.
Abstract
Hereditary spastic paraplegias (HSPs) are a group of rare, inherited, neurological diseases characterized by broad clinical and genetic heterogeneity. Lower-limb spasticity with first motor neuron involvement is the core symptom of all HSPs.
As spasticity is a syndrome and not a disease, it develops on top of other neurological signs (ataxia, dystonia, and parkinsonism). Indeed, the definition of genes responsible for HSPs goes beyond the 79 identified SPG genes. In order to avoid making a catalog of the different genes involved in HSP in any way, we have chosen to focus on the HSP with cerebellar ataxias since this is a frequent association described for several genes. This overlap leads to an intermediary group of spastic ataxias which is actively genetically and clinically studied. The most striking example is SPG7, which is responsible for HSP or cerebellar ataxia or both.
There are no specific therapies against HSPs, and there is a dearth of randomized trials in patients with HSP, especially on spasticity when it likely results from other mechanisms. Thus far, no gene-specific therapy has been developed for HSP, but emerging therapies in animal models and neurons derived from induced pluripotent stem cells are potential treatments for patients.
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SOURCE: Fac Rev. 2021 Mar 10;10:27. doi: 10.12703/r/10-27. eCollection 2021. PMID: 33817696 Copyright: © 2021 Durr A et al.
Recent advances in understanding hereditary spastic paraplegias and emerging therapies
Pauline Lallemant-Dudek 1 , Frederic Darios 1 , Alexandra Durr 1 2
1. Paris Brain Institute (ICM), Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France.
2. Assistance Publique-Hôpitaux de Paris (AP-HP), Genetic Department, Pitié-Salpêtrière University Hospital, Paris, France.