Antiretroviral therapy in sporadic adult amyotrophic lateral sclerosis

Westarp, M.E.; Bartmann, Peter; Rößler, Jochen; Geiger, Elisabeth; Westphal, K. P.; Schreiber, Herbert; Fuchs, Dietmar; Westarp, Maria P.; Kornhuber, H. H.

doi:10.1097/00001756-199306000-00056

Cited by 24 publications

(8 citation statements)

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“…In the 1990s, antibodies against foamy viruses were detected in serum of SALS patients (Alfahad and Nath, 2013) and a clinical study was initiated to treat SALS patients positive for antibodies against the foamy virus human spuma retrovirus (HSRV), with zidovudine, though it showed no clinical benefit (Westarp et al, 1993). Later, the implication of HSRV in ALS patients was challenged (Rosener et al, 1998) and currently foamy viruses are not considered to participate in ALS (Alfahad and Nath, 2013).…”

Section: Antiretrovirals Therapy For Alsmentioning

confidence: 99%

A chemogenomic approach seems indispensable for effective treatment of amyotrophic lateral sclerosis

Pampalakis

Angelis

Kastana

et al. 2021

Preprint

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ALS is a fatal untreatable disease involving degeneration of motor neurons. Μultiple causative genes encoding proteins with versatile functions have been identified indicating that diverse biological pathways lead to ALS. Gene and stem cell-based therapies are not expected to enter clinical practice anytime soon. Thus, chemical entities represent a promising choice to delay ALS progression, attenuate symptoms and/or increase life expectancy. Various compounds proved effective in transgenic models overexpressing distinct ALS causative genes but showed no efficacy in clinical trials. Notably, while animal models provide a uniform genetic background for preclinical testing, ALS patients are not stratified, and the distinct genetic forms of ALS are treated as a unique group which could explain the discrepancy between treating genetically homogeneous mice and quite heterogeneous patient cohorts. We suggest that chemical entity-genotype correlation should be exploited to guide patient stratification for therapy.

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Section: Antiretrovirals Therapy For Alsmentioning

confidence: 99%

A chemogenomic approach seems indispensable for effective treatment of amyotrophic lateral sclerosis

Pampalakis

Angelis

Kastana

et al. 2021

Preprint

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“…The first trial was an open-label pilot trial in which 10 PALS each took the NRTI zidovudine between 2 and 12 months. While serum creatine kinase (total CK) levels dropped coincident with treatment, ''clinical courses were not significantly altered'' (48). This trial utilized an ARV that has excellent penetrance into the CNS (49) and has been reported to be active in vitro against HERV (38,39); however, the trial design was flawed in that it enrolled a very small number of PALS, followed them for variable amounts of time, and used unclear clinical outcome measures.…”

Section: Trialsmentioning

confidence: 99%

“…Both above-mentioned clinical trials in PALS suggested that the side effect profile of two different ARVs in monotherapy is similar between PALS and patients with HIV (48,50); but it is unknown if this extends to other ARVs. In the zidovudine trial, none of the 12 PALS discontinued treatment due to side effects; however, it was not reported if there were any side effects experienced by these PALS (48). Common side effects experienced by patients taking zidovudine for HIV infection include headache, malaise, anorexia, nausea, and vomiting (53).…”

Section: Risksmentioning

confidence: 99%

ALSUntangled 45: Antiretrovirals

2018

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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“…In fact, because of the potential reversibility of ALS in HIV infected patients, testing for concomitant HIV infection in every sALS case is warranted in any individual with risk for HIV infection, especially due to difficulty in separating sALS from HALS on clinical grounds alone. Trials in HIV-negative sALS cases with zidovudine (Westarp et al, 1993c) and indinavir (Scelsa et al, 2005) were unsuccessful. It’s important to note that ART, specifically stavudine, has been associated with a rare but life-threatening disorder called HIV-associated neuromuscular weakness syndrome (HANWS).…”

Section: Als-like Syndromes In Patients Infected With Exogenous Rementioning

confidence: 99%

Retroviruses and amyotrophic lateral sclerosis

2013

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Amyotrophic lateral sclerosis (ALS) is a progressive, invariably fatal neurologic disorder resulting from upper and lower motor neuron degeneration, which typically develops during the sixth or seventh decade of life, and is diagnosed based on standard clinical criteria. Its underlying cause remains undetermined. The disease may occur with increased frequency within certain families, often in association with specific genomic mutations, while some sporadic cases have been linked to environmental toxins or trauma. Another possibility, first proposed in the 1970s, is that retroviruses play a role in pathogenesis. In this paper, we review the published literature for evidence that ALS is associated either with infection by an exogenous retrovirus or with the expression of human endogenous retroviral (HERV) sequences in cells of the central nervous system. A small percentage of persons infected with the human immunodeficiency virus-1 (HIV-1) or human T cell leukemia virus-1 (HTLV-1) develop ALS-like syndromes. While HTLV-1 associated ALS-like syndrome has several features that may distinguish it from classical ALS, HIV-infected patients may develop neurological manifestations that resemble classical ALS although it occurs at a younger age and they may show a dramatic improvement following the initiation of antiretroviral therapy. However, most patients with probable or definite ALS show no evidence of HIV-1 or HTLV-1 infection. In contrast, recent reports have shown a stronger association with HERV, as analysis of serum samples, and postmortem brain tissue from a number of patients with a classical ALS has revealed significantly increased expression of HERV-K, compared to controls. These findings suggest that endogenous retroviral elements are involved in the pathophysiology of ALS, but there is no evidence that they are the primary cause of the syndrome.

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Antiretroviral therapy in sporadic adult amyotrophic lateral sclerosis

Cited by 24 publications

References 0 publications

A chemogenomic approach seems indispensable for effective treatment of amyotrophic lateral sclerosis

A chemogenomic approach seems indispensable for effective treatment of amyotrophic lateral sclerosis

ALSUntangled 45: Antiretrovirals

Retroviruses and amyotrophic lateral sclerosis

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