Reaching a community in need: helping patients with PANS

22.02.2021
Patient stories
Annual Report 2020

A very challenging disease to treat

“The PANS diagnosis was missed by infectious disease specialists and neurologists at the hospital. In fact, several of the neurologists didn’t believe in PANS or PANDAS,” recalls Carrie, Avery’s mother.

Learn more about Avery’s story below

It is estimated that up to one in 200 children have paediatric acute-onset neuropsychiatric syndrome (PANS), characterised by sudden onset of obsessive-compulsive disorder (OCD) symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioural, or neurological symptoms. The medical options to treat this rare disease remain limited but immunomodulation with intravenous immunoglobulin (IVIg) seems to offer a real breakthrough.

“Before this all started, our daughter was a happy and energetic toddler. In fact, she was the easiest of our three children as a baby – we had no hint of any of the problems to come,” recalls Avery’s mother Carrie. Then suddenly, at the age of three, Avery started exhibiting extreme obsessive-compulsive symptoms, separation anxiety and severe sensory sensitivities.

“During the initial onset, Avery’s symptoms were so severe that we could not touch her clothing,” remembers Carrie, adding: “If we did, she would rub them and panic about them ‘bunching’, and often we just had to allow her to change her clothes, over and over. This could mean 20 or more changes a day. It was a terrifying experience because we had no idea what was wrong, and it was very obvious that she was also extremely scared.”

PANS/PANDAS explained

What is PANS/PANDAS ?

Paediatric acute-onset neuropsychiatric syndrome (PANS) is a neuroinflammatory encephalitis affecting children which can have various triggers. The triggers initiate a misdirected immune response resulting in the brain’s inflammation.

Paediatric autoimmune neuropsychiatric disorders associated with streptococcal disease (PANDAS) is a subset of PANS, specifically triggered by a streptococcal infection.

81% of the infections are associated with streptococcus, while 19% are from other sources.

  1. Exposure to infection

  2. Immune response launched

  3. Antibodies attack basal ganglia

  4. Sudden onset of OCD, tics, anxiety, etc.

A very challenging disease to treat

PANS appears to occur when a trigger – such as an infection or toxin – initiates a misdirected immune response resulting in inflammation of a child’s brain. This can lead to symptoms such as OCD, severe restrictive eating, anxiety, tics, personality changes, decline in mathematical and handwriting abilities, and sensory sensitivities.

At the age of six, Avery was hospitalised for four days due to an extreme flare up in her symptoms following multiple viral and bacterial infections whilst in her first year of elementary school. During this flare up, she experienced extreme OCD symptoms, severe separation anxiety, and sensory sensitivity related to touch, clothing and sound. Her food restriction was so severe that she literally lived on homemade fruit smoothies and one or two other items. Avery missed three months of school and was unable to leave home for two months following her hospitalisation. It was a distressing time for the whole family as they watched the illness take over Avery’s body and mind.

“The PANS diagnosis was missed by infectious disease and neurologists at the hospital. In fact, several of the neurologists at the hospital didn’t believe in PANS or PANDAS,” recalls Carrie. Avery wasn’t officially diagnosed until April 2019 when she was seen by a paediatrician with knowledge of PANS and the related Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). Lab results showed evidence of past and active infection with mycoplasma, a known PANS trigger. To further support the diagnosis, she also underwent a Cunningham Panel blood test which showed elevations in four out of the five categories. “Up until that time, doctors had failed to identify the condition because her strep titres were not elevated, and other potential triggers were unknown to her regular paediatrician”.

Avery was treated with antibiotics for approximately eight months as well as given multiple supplements to help boost her immune system. Her worst symptoms did improve with antibiotics; however, she continues to have flare ups when exposed to infections. Carrie explains: “We are still seeing doctors specialising in PANS/PANDAS to determine the best treatment for Avery, and we pray that one day she will be fully healed.”

Dr Roger H. Kobayashi explains:

“The search for safe and effective therapies for PANS has been difficult, but there is strong evidence that immunomodulation can mitigate or cure this disease. Intravenous immunoglobulin (IVIg) has been used in prior studies and shown significant efficacy.”

Avery was treated with antibiotics for approximately eight months as well as given multiple supplements to help boost her immune system.

Finding a way forward for patients

While IVIg is not a new therapy for PANS, there is a lack of adequate data to validate its safety and effectiveness to regulators such as the US FDA. Consequently, it is not covered by most insurance companies and is financially out of reach for many families. To help solve this, Octapharma is supporting studies into the role of IVIg as an immunomodulatory drug for the management of PANS.

In an investigator-initiated trial in 2019 led by Dr Isaac Melamed, Dr Roger H. Kobayashi and Dr Maeve E. O'Connor funded by Octapharma, the research team tested the hypothesis that PANS is related to an immune dysfunction, representing a new form of post-infectious autoimmunity. Based on this, a multi-site, open-label study was designed to explore the efficacy of a novel IVIg treatment regimen.

The results of the trial were promising. As Dr Melamed put it: “In PANS, which may be associated with an underlying immune dysregulation, sequential infusions of IVIg, subcutaneous human normal immunoglobulino, successfully ameliorated psychological symptoms and dysfunction, with sustained benefits for at least eight weeks and up to 46 weeks in a subset of subjects. In addition, baseline immune and autoimmune profiles demonstrated significant elevations in a majority of subjects, which requires further evaluation, characterisation and study to clarify the potential immune dysfunction by which PANS manifests and progresses.”

PANS/PANDAS symptoms

PANS/PANDAS symptoms are:

  • Sudden onset of obsessive compulsive disorders (OCD) and/or tic disorders

  • Severe eating restrictions

Additionally, at least two comorbid symptoms are present:

  • Anxiety, emotional liability or depression

  • Irritability

  • Aggression or severely oppositional behaviours

  • Deterioration in school performance

  • Sensory or motor abnormalities

  • Somatic signs and symptoms – e.g. sleep disturbances, enuresis

An ongoing battle

In September 2020, Octapharma launched a phase III, multicentre superiority study of a trial to evaluate whether our human normal immunoglobulin solution for intravenous administration / infusion is superior to a placebo (0.9% w/v sodium chloride) for reducing the severity of symptoms associated with PANS. The study further aims to determine the sustainability of the reduction of the severity of symptoms in children treated with Octapharma’s intravenous human normal immunoglobulin and to assess its efficacy in reducing functional impairment associated with PANS.

Researchers aim to enroll 92 patients with a confirmed diagnosis of moderate to severe PANS. Approximately 30 study sites are planned for this prospective, randomised, double-blind, placebo-controlled superiority study.

“Octapharma is proud to sponsor this important research and we are hopeful that our medicines can make a difference in the lives of children and adolescents impacted by the syndrome,” concludes Huub Kreuwel, Vice President, Scientific & Medical Affairs, Octapharma USA.

News of this research and emerging studies in the field is a source of cautious optimism for parents like Carrie. “The studies we’re hearing about, and the treatments being offered are potentially life-changing for families like ours. This trial offers hope that we may eventually have firm evidence of the safety and effectiveness of IVIg for treating this condition that has, in many ways, stolen our daughter’s childhood.”

Avery (centre) with her older sister (left) and mother, Carrie (right).
Infographics adapted from

https://www.nimh.nih.gov/health/publications/pandas/index.shtml

http://pandasnetwork.org/

Thienemann, Margo, et al. “Clinical management of pediatric acute-onset neuropsychiatric syndrome: part I—psychiatric and behavioral interventions.” Journal of child and adolescent psychopharmacology 27.7 (2017): 566-573.

Keywords

Annual report

Diseases & therapies

Immunology