`Off target' metabolic effects of anti-inflammatory drugs used for
autoimmune disorders needs better treatment strategy

Date:
January 18, 2022
Source:
University College London
Summary:
New therapies for autoimmune rheumatic diseases (AIRDs) that
are designed to better regulate lipid (fat) metabolism, could
significantly reduce the harmful side-effects caused by conventional
treatments, finds a new large-scale review.



FULL STORY ==========================================================================
New therapies for autoimmune rheumatic diseases (AIRDs) that are designed
to better regulate lipid (fat) metabolism, could significantly reduce
the harmful side-effects caused by conventional treatments, finds a new large-scale review led by UCL researchers.


========================================================================== AIRDs affect millions globally and include rheumatoid arthritis, lupus
and Sjo"gren's syndrome -- all with high rates of morbidity. They occur
when the immune system mistakenly attacks and damages its own tissues,
though the pathogenesis (the mechanism which triggers this) is still ill-defined and delivering targeted therapeutic strategies is challenging.

As a result, current treatments for AIRDs are primarily designed to
supress the symptoms (inflammation), but are 'low target' meaning the
drugs may also have unintended side-effects. In this regard, AIRDs drugs
often cause changes to cell metabolism (such as lipid metabolism) and
function, putting patients at greater risk of co-morbidities such as cardiovascular disease (CVD).

Lead author Dr George Robinson (Centre for Rheumatology Research, UCL
Division of Medicine) said: "While the mechanisms that cause rheumatic
diseases are ill- defined, some recent research indicates cell metabolism
may play an important role in triggering or worsening their onset
or affect.

"In this review we therefore sought to understand the effect of both conventional and emerging therapies on lipid metabolism in patients
with AIRDs." For the study, published in the Journal of Clinical Investigation, researchers carried out a literature review of more
than 200 studies, to assess and interpret what is known regarding the on-target/off-target (adverse) effects and mechanisms of action of current
AIRD therapies on lipid metabolism, immune cell function and CVD risk.

Explaining the findings, Dr Robinson said: "Our review found that current
AIRD therapies can both improve or worsen lipid metabolism, and either
of these changes could cause inflammation and increased CVD risk.

"Many conventional drugs also require cell metabolism for their conversion
into therapeutically beneficial products; however drug metabolism often involves the additional formation of toxic by-products, and rates
of drug metabolism can be different between patients." The review
noted that better control of inflammation using optimal combinations of immunosuppressive treatments, could lead to an improved metabolic/lipid
profile in AIRDs.

However, it also revealed many studies have shown that lipid lowering
drugs (such as statins) are not sufficient to reduce CVD risk in
some AIRDs, potentially because they cannot completely restore the anti-inflammatory properties Dr Robinson added: "The unfavourable
off-target adverse effects of current therapies used to treat AIRDs
provides an opportunity for optimal combination co-therapies targeting
lipid metabolism that could reduce immune complications and potential
increased CVD risk in patients.

"New therapeutic technologies and research have also highlighted
alternative metabolic pathways that can be more specifically targeted
to reduce inflammation but also to prevent undesirable off-target
metabolic consequences of conventional anti-inflammatory therapies." ========================================================================== Story Source: Materials provided by University_College_London. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. George Robinson, Ines Pineda-Torra, Coziana Ciurtin, Elizabeth
C. Jury.

Lipid metabolism in autoimmune rheumatic disease: implications
for modern and conventional therapies. Journal of Clinical
Investigation, 2022; 132 (2) DOI: 10.1172/JCI148552 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220118145927.htm

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