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PubMed This is a summary of 21 peer-reviewed journal articles Updated
Neurology

Treating Symptoms and Exploring New Options

At a Glance

ADAR-related HSP treatment focuses on improving movement and daily function with individualized physical therapy, medicines, injections, and mobility aids. JAK inhibitors are experimental; lowering interferon activity does not prove that existing nerve damage or spasticity will improve.

Managing ADAR-related HSP requires a two-pronged approach. First, doctors use established “standard of care” therapies to manage movement symptoms like muscle stiffness. Second, they may explore “emerging” treatments that target the underlying immune system “false alarm.” Because there is currently no cure that repairs existing nerve damage, the goal of all treatment is to improve daily function, reduce pain, and enhance quality of life [1][2].

Managing Movement: The Standard of Care

The foundation of management is addressing spasticity (muscle stiffness) and dystonia (involuntary twisting or contractions).

  • Physical Therapy (PT) and Stretching: A physical therapist should individualize stretching, strengthening, balance, and gait training to prevent contractures (permanently shortened muscles) [3]. Reducing tone is not always beneficial if a patient relies on that tone for transfers or standing, so plans must be highly customized [4][5].
  • Oral Medications: Baclofen is a common drug used to relax muscles [6]. While it can be helpful for mild stiffness, it can cause sleepiness, weakness, or confusion [7][8]. Sudden withdrawal from baclofen can also be dangerous.
  • Botulinum Toxin Type A (BoNT-A): Injections like Botox can be used for “focal” spasticity—stiffness in specific muscles like the calves or inner thighs [3]. These injections work best when followed by intensive stretching or therapy, but the effects are temporary and typically wear off after three to four months [9][10].
  • Orthotics and Aids: Braces (AFOs), walkers, or other mobility aids are used to improve alignment, save energy, and make walking safer [5][11].
  • Intrathecal Baclofen (ITB): For severe stiffness that does not respond to pills, a small pump can be surgically implanted to deliver baclofen directly to the spinal fluid [12]. This can significantly reduce muscle tone, though it involves risks like pump or catheter complications and the emergency risk of sudden withdrawal [13][14].

(Note: Evidence for BoNT-A and ITB in ADAR1 disease is extrapolated largely from general spasticity and HSP practice, rather than established specifically for this condition).

Targeting the Immune System: Emerging Options

Because ADAR-related disease involves an interferonopathy (an immune “false alarm”), researchers are studying drugs that can “turn off” the alarm system. These are considered experimental or off-label for this condition.

  • JAK Inhibitors: Drugs like ruxolitinib and baricitinib are designed to block the pathway (JAK-STAT) that triggers the interferon response [15].
  • Evidence and Limitations: Most evidence for these drugs comes from small case reports or studies of related conditions like Aicardi-Goutières Syndrome (AGS). While these drugs can improve systemic symptoms (like skin rashes or overall inflammation) and lower “interferon scores” in the blood, lowering an interferon score does not prove that existing neurological damage or spasticity will improve [16][17][18].
  • Steroids: In some cases, doctors may use corticosteroids (like dexamethasone) for a specific, clinician-defined inflammatory indication, rather than as a routine option for isolated spasticity [19][20].

Risks and Monitoring

Using “immunomodulators” (drugs that change the immune system) carries significant risks that must be balanced against potential benefits:

  • Infections: These drugs can severely impair the body’s ability to fight bacteria and viruses, risking serious infections and viral reactivation [18].
  • Blood Changes: Monitoring for low absolute neutrophil counts (neutropenia, which drastically increases infection risk) or anemia is required [21].
  • Uncertainty and Other Risks: Because ADAR-related HSP is so rare, it is not yet known which patients will respond best to these treatments. JAK inhibitors also carry warnings for thrombosis, cardiovascular events, and liver abnormalities [15].

Your care team—which should ideally include a neurologist, a physical medicine specialist (physiatrist), and sometimes an immunologist—will work with you to decide which of these tools fits your specific needs and goals [1].

Common questions in this guide

How is muscle stiffness treated in ADAR-related HSP?
Treatment may combine individualized physical therapy and stretching with baclofen, botulinum toxin injections, orthotics, mobility aids, or an intrathecal baclofen pump for severe cases. The right approach depends on whether stiffness helps with standing or transfers, so reducing muscle tone is not always beneficial in every situation.
What should I know before starting baclofen for ADAR-related HSP?
Baclofen can ease muscle stiffness but may cause sleepiness, weakness, or confusion. It should not be stopped suddenly because abrupt withdrawal can be dangerous; dose changes should be guided by the treating clinician and tied to a specific functional goal.
How long do botulinum toxin injections help with spasticity?
Botulinum toxin type A can reduce focal stiffness in selected muscles, such as the calves or inner thighs. Its effects are temporary and commonly wear off after about three to four months, and follow-up stretching or physical therapy is important.
Can JAK inhibitors repair neurological damage from ADAR-related HSP?
JAK inhibitors such as ruxolitinib and baricitinib are experimental or off-label for ADAR-related HSP. They may reduce systemic inflammation or an interferon score in some patients, but a lower score does not prove that existing nerve damage or spasticity will improve.
What monitoring is needed with experimental immune treatments?
Immune-modifying medicines require monitoring for serious infections, viral reactivation, low neutrophil counts, anemia, and other blood changes. JAK inhibitors may also carry risks involving blood clots, cardiovascular events, and the liver, so clinicians may order blood tests and regular safety checks.
When might an intrathecal baclofen pump be considered?
An intrathecal baclofen pump may be considered for severe stiffness that does not respond adequately to oral medicines. It delivers baclofen into the spinal fluid but requires surgery and carries risks involving the pump or catheter, as well as a potentially dangerous withdrawal emergency if delivery stops suddenly.

Get notified when new evidence is published on ADAR-related hereditary spastic paraplegia.

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References

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This page is for informational purposes only and does not constitute medical advice. Treatment decisions for ADAR-related HSP, including experimental immune therapy and safety monitoring, should be made with a neurologist and other specialists.

Guide contents ADAR-related hereditary spastic paraplegia
Research & Literature
04 Diagnostic Tests & Understanding Your Reports 06 Long-Term Monitoring & Staying Safe