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What’s New in Epilepsy Therapy Research? What’s New in Epilepsy Therapy Research? Evan Fertig, MD Director JCMC Epilepsy Center Director of Research Northeast.

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Presentation on theme: "What’s New in Epilepsy Therapy Research? What’s New in Epilepsy Therapy Research? Evan Fertig, MD Director JCMC Epilepsy Center Director of Research Northeast."— Presentation transcript:

1 What’s New in Epilepsy Therapy Research? What’s New in Epilepsy Therapy Research? Evan Fertig, MD Director JCMC Epilepsy Center Director of Research Northeast Regional Epilepsy Group Evan Fertig, MD Director JCMC Epilepsy Center Director of Research Northeast Regional Epilepsy Group

2 Outline Why is Epilepsy Research Important? Why is Epilepsy Research Important? What is a Clinical Trial? What is a Clinical Trial? Epilepsy Medications under Study at NEREG Epilepsy Medications under Study at NEREG New Surgical Approaches for Epilepsy New Surgical Approaches for Epilepsy

3 Case #1: Why Epilepsy Research is Important Todd age 15 Todd age 15 Grand mal seizures occur daily Grand mal seizures occur daily Last MD told mom nothing else to do Last MD told mom nothing else to do He is on 2 anti- seizure medications with bad side effects, doing poorly in school He is on 2 anti- seizure medications with bad side effects, doing poorly in school

4 More about Todd… One of his medication is carbamazepine which is a sodium channel blocker One of his medication is carbamazepine which is a sodium channel blocker Video-EEG: Seizures coming from multiple areas of his brain Video-EEG: Seizures coming from multiple areas of his brain MRI Brain: Normal MRI Brain: Normal

5 We learn that… Seizures began 6 months with fever Seizures began 6 months with fever Seizures occur more in the summer or with vigorous exercise (gym) Seizures occur more in the summer or with vigorous exercise (gym) New genetic blood test sent: sodium channel mutation! New genetic blood test sent: sodium channel mutation!

6 What’s Todd’s Diagnosis? Dravet Syndrome Dravet Syndrome Caused by a genetic problem with a brain protein (sodium channel). This was not understood before! Caused by a genetic problem with a brain protein (sodium channel). This was not understood before! Symptoms: Bad febrile seizures, then multiple sz types, worsens with sodium channel blockers Symptoms: Bad febrile seizures, then multiple sz types, worsens with sodium channel blockers

7 And so what happened? Carbamazepine is stopped (the sodium channel blocker), Atkins Diet (like the ketogenic diet) started. Carbamazepine is stopped (the sodium channel blocker), Atkins Diet (like the ketogenic diet) started. Seizure free for 2 years Seizure free for 2 years No side effects, doing very well in school No side effects, doing very well in school

8 Progress in Epilepsy Treatment Requires Teamwork between Patients an Researchers Families agree to genetic testing (bloodwork) Dravet Mutation Found! Families with Dravet Mutation agree to participate in Diet Studies Benefit Seen! Todd’s Success with Diet treatment!

9 Key Points The better we understand the causes of epilepsy… The better we understand the causes of epilepsy… The better our treatments will be! The better our treatments will be! Clinical Research is the key but can’t happen without teamwork between patients, families, and MD’s Clinical Research is the key but can’t happen without teamwork between patients, families, and MD’s

10 What is Epilepsy? A disorder of spontaneously occurring unprovoked seizures (more than 2) A disorder of spontaneously occurring unprovoked seizures (more than 2) Seizures are electrical storms of brain cells that can cause many different symptoms Seizures are electrical storms of brain cells that can cause many different symptoms

11 How do Neurons (Brain Cells) work? Ion Channel Sodium Channel: Excites! Potassium, Choride Channel: Rests!

12 What causes Seizures? Ion Channel Problems Brain Tumors, Scar tissue, etc. Excessive firing SEIZURE

13 How Do Seizure Medication Work? Close Sodium Channels (CBZ) Open Chloride Channels (gabapentin) Block release Excessive firing SEIZURE

14 What are the Limits of Medical Therapy? Trial and Error Trial and Error Brain Side Effects Brain Side Effects Body Side Effects Body Side Effects

15 Seizure Control

16 How do We Move Forward? Basic Science Clinical Trials FDA Approval- Medication available for public

17 Clinical Trials What is a clinical trial? What is a clinical trial? Key terms (from Epilepsy Study Consortium) Key terms (from Epilepsy Study Consortium) Randomization and ControlRandomization and Control BlindingBlinding PlaceboPlacebo

18 What Should I Know? Previous safety record of study medication or device Chance of getting it vs. placebo? How long? What to expect at each visit? Access to study agent after the trial?

19 What Are Some Promising New Medical Treatments under study at NEREG? Everyday Treatment Everyday Treatment GanaxoloneGanaxolone Lacosamide (Vimpat)Lacosamide (Vimpat) Pregabalin (Lyrica)Pregabalin (Lyrica) YKBYKB Emergency Treatment Emergency Treatment Intranasal Midazolam

20 Ganaxolone Neurosteroid Neurosteroid Derived natural hormoneDerived natural hormone New “mechanism of action”New “mechanism of action” GABA GABA Partial epilepsy Partial epilepsy Twice a day pill Twice a day pill

21 Ganaxolone (study 600) Effective Effective 20% reduction of seizure frequency on medication20% reduction of seizure frequency on medication 25% of subjects were >50% responders25% of subjects were >50% responders Side Effects Side Effects Safe in Animal Models Safe in nearly 1000 patients to date Dizziness and sleepiness are rare side effects

22 Ganaxolone vs. Placebo in the Adjunctive Treatment of Subjects with Partial Onset Seizures (POS) How safe and effective is Ganaxolone in adults with POS with poorly controlled seizures? Objective Age > 18, 3 AED, 3 or more sz per month Requirement Visits to Hackensack office. All medication, visits are provided for free + stipend Study Procedure

23 YKP3089 Unknown MOA Unknown MOA GABAGABA Sodium ChannelSodium Channel Partial epilepsy Partial epilepsy Once a day pill Once a day pill

24 YKP 3089 Effective Effective 1 early study1 early study Significant of subjects were >50% responders. 70% reduction in GTC were seen.Significant of subjects were >50% responders. 70% reduction in GTC were seen. Side Effects Side Effects Safe in Animal Models Safe in nearly 400 patients to date 2 allergic reactions 2 case confusion

25 YKP vs. Placebo in the Adjunctive Treatment of Subjects with Partial Onset Seizures (POS) How safe and effective is YPK3089 in adults with POS with poorly controlled seizures? Objective Age > 18, 3 AED, 4 or more sz per month Requirement Visits to Hackensack office. All medication, visits are provided for free + stipend Study Procedure

26 Lacosamide (Vimpat) Studies Why are we studying this medication when it is already available? Why are we studying this medication when it is already available? Learn how to use it better Learn how to use it better Learn if it can be used safely in populations not included in original research Learn if it can be used safely in populations not included in original research

27 Cognitive and Behavioral Effects of Lacosamide (Vimpat) for POS. PI- Marcelo Lancman, MD How does the new medicine Vimpat affect thinking (cognition) and mood (behavior)? Objective Age > 18, English, 2 or more sz per month Requirement Visits to Hackensack office over 36 weeks. All medications, visits, and neuropsychological testing are provided for free plus stipend Study Procedure

28 Lacosamide in Children. PI- Evan Fertig, MD How safe and effective is this medication in children with partial and generalized seizures? Objective Age > 1 mo to 18 years, 2 or more sz per month Requirement Visits to Hackensack office > 1 year. All medications, visitsare provided for free plus stipend Study Procedure

29 Effect of Lyrica on Anxiety in POS How safe and effective is Lyrica for Anxiety in Patients with poorly controlled POS? Objective Age > 18, 1-2 AEDs, not presently treated for anxiety Requirement Visits to Hackensack office over 6 weeks. All medication, visits, travel free plus stipend Study Procedure

30 Completed Studies Completed Studies New medications New medications

31 Aptiom ® (eslicarbazepine acetate) Partial Onset Seizures Partial Onset Seizures Once a day tablet Once a day tablet Carbamazepine (Tegretol) like medicine Carbamazepine (Tegretol) like medicine RashRash Liver AbnormalitiesLiver Abnormalities Low blood sodiumLow blood sodium

32 Emergency Treatment Rectal Diastat Rectal Diastat Clinically provenClinically proven Hard to giveHard to give Social StigmaSocial Stigma Can’t self administerCan’t self administer

33 Intranasal Midazolam Easy to give Easy to give Preferred route Preferred route Can be self- administered or given by caretaker Can be self- administered or given by caretaker Under study Under study

34 Intranasal Midazolam (IM) How safe and effective IM for Seizure Clusters? Objective Age 14-22, Seizure Clusters Requirement One visit to Hack ensa ck Hosp ital for test dose then follo w up visits. Trav el and med s are free Study Procedure

35 What are the Limits of Surgical Therapy? What’s on the Horizon?

36 When Do We Consider Resective Epilepsy Surgery?  Partial Epilepsy  Treatment Resistant Epilepsy  Failure to become seizure free after > 2 adequate trials of 2 AEDs used appropriately  Intolerable adverse effects of AEDs?

37 Why? Rate of Seizure Freedom with continued trials of Sz med is low (5%) Rate of Seizure Freedom with continued trials of Sz med is low (5%) Potential for injury with uncontrolled epilepsy over a lifetime is high! Potential for injury with uncontrolled epilepsy over a lifetime is high! Rate of Seizure Control with Resective Epilepsy Surgery is in comparison is high (30-80%) with a low complication rate Rate of Seizure Control with Resective Epilepsy Surgery is in comparison is high (30-80%) with a low complication rate Reduction or Elimination of Sz med is frequently possible Reduction or Elimination of Sz med is frequently possible

38 How does Epilepsy surgery work? Brain Tumors, Scar tissue, etc. Excessive firing SEIZURE

39 Epilepsy Surgery

40 Rates of Surgical Success* Temporal Lobectomy 70-80% Temporal Lobectomy 70-80% “Lesion” Resection 70-80% “Lesion” Resection 70-80% “Non-Lesional” Resection 30-50% “Non-Lesional” Resection 30-50% Medical Management 5% Medical Management 5% * Absence of Disabling Seizures

41 What are the Limits of Surgical Therapy? Small risk: bleeding and infection Small risk: bleeding and infection Not effective for all seizures types Not effective for all seizures types Not effective if seizures are come from more than one location Not effective if seizures are come from more than one location Not possible if seizures arise from critical brain tissue (hand area) Not possible if seizures arise from critical brain tissue (hand area)

42 Visualase Laser Treatment Evaluation is same as for epilepsy surgery No need for open brain operation

43 Visualase Implant Probe inserted in OR Transferred to MRI Treatment Laser Treatment MRI monitors safety of Laser Rx real-time Follow up Probe Removed Patient can leave same day

44 Neuromodulatory Treatments Device implanted to alter instead of destroy brain tissue Device implanted to alter instead of destroy brain tissue Range of treatment possible: Electrical, Cooling, local medications Range of treatment possible: Electrical, Cooling, local medications Limit body/brain side effectsLimit body/brain side effects Improve brain function? Improve brain function?

45 NeuroPace Implant Device under skull Leads to seizure focus Treatment Detects seizure Electrical treatment delivered Follow up MD reviews Fine tunes treatment

46 What will Epilepsy Care Look Like in Future? Personalized Medical Choices based on genetics Personalized Medical Choices based on genetics Truly Anti-epileptic therapy Truly Anti-epileptic therapy Treatment directed right at the seizure focus Treatment directed right at the seizure focus

47 Conclusion In most cases, seizures can be well controlled with medications with minimal side effects In most cases, seizures can be well controlled with medications with minimal side effects The correct diagnosis to guide treatment is essential The correct diagnosis to guide treatment is essential Epilepsy is more than just seizures, and the treatment may require a team approach Epilepsy is more than just seizures, and the treatment may require a team approach

48 Conclusion Some cases are more difficult to control, and treatment with diet therapy or surgery may be used, or clinical trials may be an option Some cases are more difficult to control, and treatment with diet therapy or surgery may be used, or clinical trials may be an option

49 Please Contact Us for More Information! Director of Research Evan Fertig, MD Director of Research Evan Fertig, MD Evan Fertig, MD Evan Fertig, MD Clinical Research Coordinator Munazza Malik, MD (201) Clinical Research Coordinator Munazza Malik, MD (201) Munazza Malik, MD Munazza Malik, MD


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